Interface zone fibroblasts play key role in gastric cancer

Interface zone fibroblasts (INFs) in gastric adenocarcinoma promote the invasion, migration, and proliferation of cancer cells, as well as prevent apoptosis, to a greater degree than normal or tumor zone fibroblasts, say researchers.

The findings, published in the Journal of Clinical Pathology, suggest that INFs may play an important role in the progression and metastasis of gastric cancer.

The team, led by Li-Feng Wang, from JiaoTong University School of Medicine in Shanghai, China, adds: "Targeting INFs may therefore be a therapeutic strategy for the treatment of gastric cancer that warrants further study. INFs may be a good surrogate marker for cancer progression and invasion and serve as a tool for post-treatment surveillance."

For the study, the researchers isolated primary fibroblasts from the distal normal zone, the interface zone, and the tumor zone of 60 gastric carcinoma tissue samples, alongside which 20 normal gastric tissue samples were studied.

In addition, a series of experiments were conducted in which MGC-803 gastric cancer cell lines were used to compare the cell migration and invasion potential of each fibroblast type, as well as their ability to induce cell proliferation and prevent apoptosis.

The results showed that there was no fibroblast activation protein (FAP) expression in normal gastric cancer tissue. However, expression was significantly greater in the gastric cancer invasion front than in other sites of gastric cancer tissue, at 31.83% versus 22.65%.

Also, FAP expression was greater in stage III-IV than stage I-II disease, at 30.16% versus 19.37%, and was greater in INFs than in normal zone fibroblasts (NFs) and tumor zone fibroblasts (CFs).

The cell line experiments revealed that co-cultivation with INFs led to an 8.45-fold and 1.89-fold increase in MGC-803 cell invasion compared with co-cultivation with NFs and CFs, respectively. Migration of MGC-803 cells was also increased 4.91-fold and 1.92-fold by co-cultivation with INFs compared with NF and CF co-cultivation, respectively.

Furthermore, MGC-803 cells cultured in INF-conditioned medium (CM) grew more rapidly, had a greater number of proliferations at all time points, and were significantly less likely to undergo apoptosis than those cultured in NF- or CF-CM.

"Thus, INFs possess a greater capacity to interact with and to modulate the gastric cancer cell model system than NFs or CAFs," the team writes. "Signal crosstalk between the cancer cells and INFs may direct the modification of the adjacent ECM [extracellular matrix] and basement membrane."

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